Graham Dustin M, Wong Kwoon Y, Shapiro Peter, Frederick Courtney, Pattabiraman Kartik, Berson David M
Department of Neuroscience, Brown University, Providence, RI 02912, USA.
J Neurophysiol. 2008 May;99(5):2522-32. doi: 10.1152/jn.01066.2007. Epub 2008 Feb 27.
Intrinsically photosensitive retinal ganglion cells (ipRGCs) are photoreceptors of the mammalian eye that drive pupillary responses, synchronization of circadian rhythms, and other reflexive responses to daylight. Melanopsin is the ipRGC photopigment, but the signaling cascade through which this invertebrate-like opsin triggers the photocurrent in these cells is unknown. Here, using patch-clamp recordings from dissociated ipRGCs in culture, we show that a membrane-associated phosphoinositide cascade lies at the heart of the ipRGC phototransduction mechanism, similar to the cascade in rhabdomeric photoreceptors of invertebrate eyes. When ipRGCs were illuminated, melanopsin activated a G protein of the G(q/11) class, stimulating the effector enzyme phospholipase C. The presence of these signaling components in ipRGCs was confirmed by single-cell RT-PCR and immunofluorescence. The photoresponse was fully functional in excised inside-out patches of ipRGC membrane, indicating that all core signaling components are within or tightly coupled to the plasma membrane. The striking similarity of phototransduction in ipRGCs and invertebrate rhabdomeric photoreceptors reinforces the emerging view that these cells have a common evolutionary origin.
内在光敏性视网膜神经节细胞（ipRGCs）是哺乳动物眼睛中的光感受器，可驱动瞳孔反应、昼夜节律同步以及对日光的其他反射反应。黑视蛋白是ipRGC的光色素，但这种类似无脊椎动物的视蛋白触发这些细胞中光电流的信号级联尚不清楚。在这里，我们使用培养的解离ipRGC进行膜片钳记录，结果表明膜相关磷酸肌醇级联是ipRGC光转导机制的核心，类似于无脊椎动物眼睛的视杆光感受器中的级联。当ipRGC受到光照时，黑视蛋白激活G(q/11)类G蛋白，刺激效应酶磷脂酶C。单细胞逆转录聚合酶链反应（RT-PCR）和免疫荧光证实了ipRGC中这些信号成分的存在。光反应在切除的ipRGC膜的内翻膜片中完全发挥功能，这表明所有核心信号成分都在质膜内或与质膜紧密耦合。ipRGC和无脊椎动物视杆光感受器中光转导的惊人相似性强化了这样一种新出现的观点，即这些细胞有共同的进化起源。
